Blood coagulation is important for the elaboration of cellular immune reactions is involved in the growth and metastasis of malignant tumors in experimental animals and man. Although the exact mechanism(s) responsible for the activation f coagulation in these disorders is not known, recent evidence suggests that leukocyte-related proco agulants may play a role. This evidence can be summarized as follows: Monocyte tissue factor (MTF), a cell-associated lipophilic procoagulant, is generated in increased amounts in delayed hypersensitivity reactions and in cancer. Moreover, a close correlation exists between the rate of in vivo clotting and the amount of MTF activity generated by cells from cancer patients. Conversely, defective delayed hypersensitivity reactions and tumor growth inhibition are observed when MTF generation is inhibited. The anticoagulant sodium warfarin impairs MTF generation, impairs the development of DH and impairs tumor growth. This project will investigate the relationship between MTF generation, inflammatory reactions and tumor growth using in vitro and in vivo model systems. Two in vitro models of TF generation, the U937 macrophage-like cell line and a fibroblast cell line, will be characterized and used to examine serum or cell-associated products which can stimulate increased TF generation. A guinea pig model will be used to examine the relationship between MTF generation, activation of the immune response and tumor growth. These models will also be utilized to define the mechanism of inhibition of MTF generation by sodium warfarin. These studies may provide information regarding the mechanisms involved in the activation of coagulation in inflammation and neoplasia. A better understanding of these mechanisms and the potential pharmacologic modification of MTF generation may lead to more effect treatment of these disorders.